Circadian rhythmicity of mammals is regulated primarily by photoperiod interacting with a clock in the brain. This clock, the suprachiasmatic nucleus (SCN), times the expression of physiological and behavior events that repeat approximately every 24 hr. Light information reaches the SCN directly via a retinohypothalamic tract and indirectly via a geniculohypothalamic tract. The latter is derived from NPY and other, presently unidentified, cell types in the intergeniculate leaflet (IGL). In addition, there is extensive innervation of the IGL and SCN by serotonergic cells of the midbrain raphe nuclei. Destruction of these cells substantially modifies the expression of hamster circadian rhythmicity. The present set of experiments will elucidate the neuroanatomy of this system and the extent to which it controls the circadian locomotor rhythm. The specific aims include: a) delineation of the raphe cells and their neuromodulator type projecting to SCN, IGL and superior colliculus; b) description of the circuitry involving the enkephalinergic cells of the IGL and VLG and their contribution to the geniculohypothalamic tract; c) determination of the extent to which the neurotransmitter, serotonin, regulates circadian rhythm phase, period or magnitude by acting through the IGL or SCN; d) direct confirmation that serotonin is the transmitter acting through specific receptors to regulate the circadian rhythm system. Immunohistological and immunohistofluorescent methods will identify cells and fibers. Receptor autoradiography will identify serotonergic receptor types in the SCN and IGL. The neurotoxins, N-methyl-d-aspartate and 5,7- dihydroxytryptamine, will be used to make lesions of elements of the neural system under investigation. An understanding of the basic neuroanatomy of the circadian rhythm system will facilitate development of behavioral and pharmacological therapies for the treatment of circadian rhythm-based sleep disorders and mental health pathologies.